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Ruyi Gao; Huafen Zheng; Kaituo Liu; Zhuxing Ji; Miao Cai; Min Gu; Jiao Hu; Xiaowen Liu; Shunlin Hu; Xiaoquan Wang; Xiufan Liu. Genesis, evolution and host species distribution of influenza A (H10N3) virus in China. Journal of Infection 2021, 1 .
AMA StyleRuyi Gao, Huafen Zheng, Kaituo Liu, Zhuxing Ji, Miao Cai, Min Gu, Jiao Hu, Xiaowen Liu, Shunlin Hu, Xiaoquan Wang, Xiufan Liu. Genesis, evolution and host species distribution of influenza A (H10N3) virus in China. Journal of Infection. 2021; ():1.
Chicago/Turabian StyleRuyi Gao; Huafen Zheng; Kaituo Liu; Zhuxing Ji; Miao Cai; Min Gu; Jiao Hu; Xiaowen Liu; Shunlin Hu; Xiaoquan Wang; Xiufan Liu. 2021. "Genesis, evolution and host species distribution of influenza A (H10N3) virus in China." Journal of Infection , no. : 1.
Since the influenza pandemic occurred in 1918, people have recognized the perniciousness of this virus. It can cause mild to severe infections in animals and humans worldwide, with extremely high morbidity and mortality. Since the first day of human discovery of it, the “game” between the influenza virus and the host has never stopped. NS1 protein is the key protein of the influenza virus against host innate immunity. The interaction between viruses and organisms is a complex and dynamic process, in which they restrict each other, but retain their own advantages. In this review, we start by introducing the structure and biological characteristics of NS1, and then investigate the factors that affect pathogenicity of influenza which determined by NS1. In order to uncover the importance of NS1, we analyze the interaction of NS1 protein with interferon system in innate immunity and the molecular mechanism of host antagonism to NS1 protein, highlight the unique biological function of NS1 protein in cell cycle.
Zhu-Xing Ji; Xiao-Quan Wang; Xiu-Fan Liu. NS1: A Key Protein in the “Game” Between Influenza A Virus and Host in Innate Immunity. Frontiers in Cellular and Infection Microbiology 2021, 11, 670177 .
AMA StyleZhu-Xing Ji, Xiao-Quan Wang, Xiu-Fan Liu. NS1: A Key Protein in the “Game” Between Influenza A Virus and Host in Innate Immunity. Frontiers in Cellular and Infection Microbiology. 2021; 11 ():670177.
Chicago/Turabian StyleZhu-Xing Ji; Xiao-Quan Wang; Xiu-Fan Liu. 2021. "NS1: A Key Protein in the “Game” Between Influenza A Virus and Host in Innate Immunity." Frontiers in Cellular and Infection Microbiology 11, no. : 670177.
Avian influenza virus (AIV) H7N9 that emerged in 2013 in eastern China is a novel zoonotic agent mainly circulating in poultry without clinical signs but causing severe disease with high fatality in humans in more than 5 waves. Since the emergence of highly pathogenic (HP) H7N9 variants in 2016, it has induced heavy losses in the poultry industry leading to the implementation of an intensive nationwide vaccination program at the end of wave 5 (September 2017). To characterize the ongoing evolution of H7N9 AIV, we conducted analyses of H7N9 glycoprotein genes obtained from 2013 to 2019. Bayesian analyses revealed a decreasing population size of HP H7N9 variants post wave 5. Phylogenetic topologies revealed that two novel small subclades were formed and carried several fixed amino acid mutations that were along HA and NA phylogenetic trees since wave 5. Some of the mutations were located at antigenic sites or receptor binding sites. The antigenic analysis may reveal a significant antigenic drift evaluated by hemagglutinin inhibition (HI) assay and the antigenicity of H7N9 AIV might evolute in large leaps in wave 7. Molecular simulations found that the mutations (V135T, S145P, and L226Q) around the HA receptor pocket increased the affinity to α2,3-linked sialic acid (SIA) while decreased to α2,6-linked SIA. Altered affinity may suggest that HP H7N9 variations aggravate the pathogenicity to poultry but lessen the threat to public health. Selection analyses showed that the HP H7N9 AIV experienced an increasing selection pressure since wave 5, and the national implementation of vaccination might intensify the role of natural selection during the evolution waves 6 and 7. In summary, our data provide important insights about the genetic and antigenic diversity of circulating HP H7N9 viruses from 2017 to 2019. Enhanced surveillance is urgently warranted to understand the current situation of HP H7N9 AIV.
Dongchang He; Jinyuan Gu; Min Gu; Huiguang Wu; Juan Li; Tiansong Zhan; Yu Chen; Naiqing Xu; Zhichuang Ge; Guoqing Wang; Xiaoli Hao; Xiaoquan Wang; Jiao Hu; Zenglei Hu; Shunlin Hu; Xiaowen Liu; Xiufan Liu. Genetic and antigenic diversity of H7N9 highly pathogenic avian influenza virus in China. Infection, Genetics and Evolution 2021, 93, 104993 .
AMA StyleDongchang He, Jinyuan Gu, Min Gu, Huiguang Wu, Juan Li, Tiansong Zhan, Yu Chen, Naiqing Xu, Zhichuang Ge, Guoqing Wang, Xiaoli Hao, Xiaoquan Wang, Jiao Hu, Zenglei Hu, Shunlin Hu, Xiaowen Liu, Xiufan Liu. Genetic and antigenic diversity of H7N9 highly pathogenic avian influenza virus in China. Infection, Genetics and Evolution. 2021; 93 ():104993.
Chicago/Turabian StyleDongchang He; Jinyuan Gu; Min Gu; Huiguang Wu; Juan Li; Tiansong Zhan; Yu Chen; Naiqing Xu; Zhichuang Ge; Guoqing Wang; Xiaoli Hao; Xiaoquan Wang; Jiao Hu; Zenglei Hu; Shunlin Hu; Xiaowen Liu; Xiufan Liu. 2021. "Genetic and antigenic diversity of H7N9 highly pathogenic avian influenza virus in China." Infection, Genetics and Evolution 93, no. : 104993.
Pigeon paramyxovirus type 1 (PPMV-1) is an antigenic variant of Newcastle disease virus (NDV) which is mainly associated with infections of pigeons and has the potential to result in disease in chickens. In this study, we characterised 21 PPMV-1 isolates from diseased pigeons in China during 2007–2019. Phylogenetic analysis revealed that all isolates belonged to genotype VI. Among them, most isolates belonged to sub-genotype VI.2.1.1.2.2, suggesting that VI.2.1.1.2.2 has become a prevalent genotype in pigeons in China. The results showed that all PPMV-1 isolates were mesogenic in nature according to the mean death time (MDT) and intracerebral pathogenicity index (ICPI). In vitro and in vivo studies demonstrated that two genetically closely related isolates (Pi-11 and Pi-10) both of which belonged to sub-genotype VI.2.1.1.2.2 had similar replication kinetics in cells derived from pigeons, while the replication titre of Pi-11 was significantly higher than that of Pi-10 in cells derived from chickens. Pi-11 and Pi-10 could contribute to morbidity and mortality in pigeons. Remarkably, although the two viruses resulted in no apparent disease symptom in chickens, Pi-11 could cause more severe histopathological lesions and had a stronger replication ability in chickens compared to Pi-10. Moreover, chickens infected with Pi-11 had higher shedding efficiency than chickens infected with Pi-10. Additionally, several mutations within important functional regions of the fusion (F) and haemagglutinin-neuraminidase (HN) proteins might be associated with different pathogenicity of the two viruses in chickens. Collectively, these results indicated that the Pi-11-like virus of pigeon origin has the potential to induce severe outbreaks in chicken flocks. These findings will help us better understand the epidemiology and evolution of PPMV-1 in China and serve as a foundation for the further investigation of the mechanism underlying the pathogenic difference of PPMV-1 isolates in chickens.
Tiansong Zhan; Xiaolong Lu; Dongchang He; Xiaomin Gao; Yu Chen; Zenglei Hu; Xiaoquan Wang; Shunlin Hu; Xiufan Liu. Phylogenetic analysis and pathogenicity assessment of pigeon paramyxovirus type 1 circulating in China during 2007–2019. Transboundary and Emerging Diseases 2021, 1 .
AMA StyleTiansong Zhan, Xiaolong Lu, Dongchang He, Xiaomin Gao, Yu Chen, Zenglei Hu, Xiaoquan Wang, Shunlin Hu, Xiufan Liu. Phylogenetic analysis and pathogenicity assessment of pigeon paramyxovirus type 1 circulating in China during 2007–2019. Transboundary and Emerging Diseases. 2021; ():1.
Chicago/Turabian StyleTiansong Zhan; Xiaolong Lu; Dongchang He; Xiaomin Gao; Yu Chen; Zenglei Hu; Xiaoquan Wang; Shunlin Hu; Xiufan Liu. 2021. "Phylogenetic analysis and pathogenicity assessment of pigeon paramyxovirus type 1 circulating in China during 2007–2019." Transboundary and Emerging Diseases , no. : 1.
As an oncolytic virus, Newcastle disease virus (NDV) can specifically kill tumor cells and has been tested as an attractive oncolytic agent for cancer virotherapy. Virus infection can trigger the changes of the cellular microRNA (miRNA) expression profile, which can greatly influence viral replication and pathogenesis. However, the interplay between NDV replication and cellular miRNA expression in tumor cells is still largely unknown. In the present study, we compared the profiles of cellular miRNAs in uninfected and NDV-infected HeLa cells by small RNA deep sequencing. Here we report that NDV infection in HeLa cells significantly changed the levels of 40 miRNAs at 6 h post-infection (hpi) and 62 miRNAs at 12 hpi. Among 23 highly differentially expressed miRNAs, NDV infection greatly promoted the levels of 3 miRNAs and suppressed the levels of 20 miRNAs at both time points. These 23 miRNAs are predicted to target various genes involved in virus replication and antiviral immunity such as ErbB, Jak-STAT, NF-kB and RIG-I-like receptor. Verification of deep sequencing results by quantitative RT-PCR showed that 9 out of 10 randomly selected miRNAs chosen from this 23-miRNA pool were consistent with deep sequencing data, including 6 down-regulated and 3 up-regulated. Further functional research revealed that hsa-miR-4521, a constituent in this 23-miRNA pool, inhibited NDV replication in HeLa cells. Moreover, dual-luciferase and gene expression array uncovered that the member A of family with sequence similarity 129 (FAM129A) was directly targeted by hsa-miR-4521 and positively regulated NDV replication in HeLa cells, indicating that hsa-miR-4521 may regulate NDV replication via interaction with FAM129A. To our knowledge, this is the first report of the dynamic cellular miRNA expression profile in tumor cells after NDV infection and may provide a valuable basis for further investigation on the roles of miRNAs in NDV-mediated oncolysis.
Yu Chen; Shanshan Zhu; Yuru Pei; Jiao Hu; Zenglei Hu; Xiaowen Liu; Xiaoquan Wang; Min Gu; Shunlin Hu; Xiufan Liu. Differential microRNA Expression in Newcastle Disease Virus-Infected HeLa Cells and Its Role in Regulating Virus Replication. Frontiers in Oncology 2021, 11, 1 .
AMA StyleYu Chen, Shanshan Zhu, Yuru Pei, Jiao Hu, Zenglei Hu, Xiaowen Liu, Xiaoquan Wang, Min Gu, Shunlin Hu, Xiufan Liu. Differential microRNA Expression in Newcastle Disease Virus-Infected HeLa Cells and Its Role in Regulating Virus Replication. Frontiers in Oncology. 2021; 11 ():1.
Chicago/Turabian StyleYu Chen; Shanshan Zhu; Yuru Pei; Jiao Hu; Zenglei Hu; Xiaowen Liu; Xiaoquan Wang; Min Gu; Shunlin Hu; Xiufan Liu. 2021. "Differential microRNA Expression in Newcastle Disease Virus-Infected HeLa Cells and Its Role in Regulating Virus Replication." Frontiers in Oncology 11, no. : 1.
H7N9 avian influenza vaccines induce high levels of non-neutralizing (nonNeu) antibodies against the haemagglutinin (HA). However, the antigenic epitopes underlying this particular antibody response are still undefined. In this study, a panel of 13 monoclonal antibodies (mAbs) against the HA protein of H7N9 virus was generated and 12 of them had no hemagglutination inhibition and virus neutralizing activities. One linear epitope in the stalk (373-TAA-375) recognized by three mAbs and one conformational epitope in the head (220Q-225S-227G) targeted by one mAb were identified using peptide-based enzyme-linked immunosorbent assay (ELISA) and biopanning of phage display random peptide library. In addition, competition ELISA revealed that the mAb targeting the head epitope strongly inhibited HA-binding of chicken nonNeu anti-H7N9 sera, whereas lower inhibition was observed for chicken neutralizing antisera, indicating the immunodominance of this epitope in the elicitation of nonNeu antibodies. Moreover, the stalk epitope is conserved among the H1-H17 subtypes and the mAb recognizing this epitope exhibited cross-reactivity with different subtypes. In conclusion, two novel nonNeu epitopes in H7N9 HA were identified, and an epitope in the head was identified as an immunodominant epitope underlying the induction of nonNeu H7N9 antibodies. Our results add new knowledge to the molecular basis for antibody immunity against H7N9 vaccines and provide useful implications for vaccine design and modification.
Zenglei Hu; Jiangyan Zhao; Lei Shi; Jiao Hu; Shunlin Hu; Xiufan Liu. Identification of the dominant non-neutralizing epitope in the haemagglutinin of H7N9 avian influenza virus. Virus Research 2021, 298, 198409 .
AMA StyleZenglei Hu, Jiangyan Zhao, Lei Shi, Jiao Hu, Shunlin Hu, Xiufan Liu. Identification of the dominant non-neutralizing epitope in the haemagglutinin of H7N9 avian influenza virus. Virus Research. 2021; 298 ():198409.
Chicago/Turabian StyleZenglei Hu; Jiangyan Zhao; Lei Shi; Jiao Hu; Shunlin Hu; Xiufan Liu. 2021. "Identification of the dominant non-neutralizing epitope in the haemagglutinin of H7N9 avian influenza virus." Virus Research 298, no. : 198409.
Xiaolong Lu; Xiaoquan Wang; Tiansong Zhan; Yifan Sun; Xin Wang; Naiqing Xu; Tianxing Liao; Yu Chen; Min Gu; Shunlin Hu; Xiaowen Liu; Xiufan Liu. Surveillance of Class I Newcastle Disease Virus at Live Bird Markets and Commercial Poultry Farms in Eastern China Reveals the Epidemic Characteristics. Virologica Sinica 2021, 36, 818 -822.
AMA StyleXiaolong Lu, Xiaoquan Wang, Tiansong Zhan, Yifan Sun, Xin Wang, Naiqing Xu, Tianxing Liao, Yu Chen, Min Gu, Shunlin Hu, Xiaowen Liu, Xiufan Liu. Surveillance of Class I Newcastle Disease Virus at Live Bird Markets and Commercial Poultry Farms in Eastern China Reveals the Epidemic Characteristics. Virologica Sinica. 2021; 36 (4):818-822.
Chicago/Turabian StyleXiaolong Lu; Xiaoquan Wang; Tiansong Zhan; Yifan Sun; Xin Wang; Naiqing Xu; Tianxing Liao; Yu Chen; Min Gu; Shunlin Hu; Xiaowen Liu; Xiufan Liu. 2021. "Surveillance of Class I Newcastle Disease Virus at Live Bird Markets and Commercial Poultry Farms in Eastern China Reveals the Epidemic Characteristics." Virologica Sinica 36, no. 4: 818-822.
PA-X is a novel discovered accessory protein encoded by the PA mRNA of the influenza A virus. Accumulated studies have demonstrated the crucial role of this protein in regulating the virulence of various subtypes of influenza virus, including H1N1, H5N1, H9N2, H1N2, H3N8 and H3N2 virus. However, the role of PA-X protein in regulating the virulence of the highly pathogenic avian H7N9 virus was unknown. In this study, we firstly generated two recombinant H7N9 viruses which have lower PA-X expression level than the parental H7N9 virus. We then systematically compared their difference in virus replication, polymerase activity, virulence and virus-induced host immune responses in mice. The results showed that the PA-X deficient viruses significantly increased viral replication in madin darby canine kidney cells and slightly increased viral replication in mouse lung. In addition, loss of PA-X expression significantly increased viral polymerase activity and alleviated the host-shutoff activity mediated by the parental PA protein. However, in contrast with the usual function of PA-X in regulating the virulence in different subtype influenza virus, no obvious effect on viral virulence in mice was observed by H7N9 PA-X protein. Furthermore, among the 12 kinds of cytokines and 2 kinds of complement derived components that we tested, the PA-X deficiency viruses only induced significantly higher expression levels of MX1 than the parental virus. Altogether, these results showed that PA-X has little effect on viral virulence and viral induced innate immune response of the H7N9 subtype virus. Our study adds further information for the growing understanding of the complexity of PA-X in regulating viral virulence and host innate immune response of different influenza virus.
Ming Kong; Kaibiao Chen; Zixiong Zeng; Xiaoquan Wang; Min Gu; Zenglei Hu; Xinan Jiao; Jiao Hu; Xiufan Liu. The virulence modulator PA-X protein has minor effect on the pathogenicity of the highly pathogenic H7N9 avian influenza virus in mice. Veterinary Microbiology 2021, 255, 109019 .
AMA StyleMing Kong, Kaibiao Chen, Zixiong Zeng, Xiaoquan Wang, Min Gu, Zenglei Hu, Xinan Jiao, Jiao Hu, Xiufan Liu. The virulence modulator PA-X protein has minor effect on the pathogenicity of the highly pathogenic H7N9 avian influenza virus in mice. Veterinary Microbiology. 2021; 255 ():109019.
Chicago/Turabian StyleMing Kong; Kaibiao Chen; Zixiong Zeng; Xiaoquan Wang; Min Gu; Zenglei Hu; Xinan Jiao; Jiao Hu; Xiufan Liu. 2021. "The virulence modulator PA-X protein has minor effect on the pathogenicity of the highly pathogenic H7N9 avian influenza virus in mice." Veterinary Microbiology 255, no. : 109019.
Previous studies showed that, compared to genotype IV Newcastle disease virus (NDV), genotype VII NDV induced extensive extracellular matrix (ECM) degradation by up-regulating the protein expression of matrix metalloproteinase (MMP)-14 in chicken spleens. To investigate potential relationship between MMP-14 function and the ECM degradation, an in vitro peripheral blood mononuclear cells (PBMCs) infection model was established to study the effect of genotype VII NDV (JS5/05) infection on MMP-14 expression, ECM degradation and cell transmigration. The gene and protein expression levels of MMP-14 in NDV-infected chicken PBMCs were measured by quantitative real-time PCR (qRT-PCR) and Western blot, and the subcellular location of MMP-14 was analyzed using immunofluorescence microscopy. A fluorescence-based collagen degradation assay was optimized to measure ECM degradation in PBMCs. Additionally, parameters of a transwell-based transmigration assay were also optimized to determine chemotaxis and transmigration of virus-infected PBMCs. The results showed that JS5/05 up-regulated significantly the expression of MMP-14 in PBMCs at the mRNA and protein levels compared to genotype IV NDV (Herts/33). MMP-14 was transported towards the membrane and accumulated on the cell surface of the JS5/05-infected cells, whereas it remained mainly in the cytoplasm of the Herts/33-infected cells. Collagen degradation assay showed that JS5/05-infected cells exhibited significant collagen degradation compared to the Herts/33-infected cells, and the areas of collagen degradation co-localized with cell surface MMP-14 in the JS5/05-infected cells. The transwell-based transmigration system showed that the transmigration of the JS5/05-infected PBMCs was enhanced significantly compared to the Herts/33-infected cells. These results demonstrated that genotype VII NDV induced up-regulation and surface accumulation of MMP-14 in PBMCs, leading to enhanced ECM degradation and cell migration, and the assays optimized for this study were useful for investigating the regulation of cell behaviour by NDV.
Han Gu; Zenglei Hu; Liwei Shi; Xiufan Liu. Assay of extracellular matrix degradation and transmigration of chicken peripheral blood mononuclear cells after infection with genotype VII Newcastle disease virus in vitro. Journal of Virological Methods 2021, 290, 114076 .
AMA StyleHan Gu, Zenglei Hu, Liwei Shi, Xiufan Liu. Assay of extracellular matrix degradation and transmigration of chicken peripheral blood mononuclear cells after infection with genotype VII Newcastle disease virus in vitro. Journal of Virological Methods. 2021; 290 ():114076.
Chicago/Turabian StyleHan Gu; Zenglei Hu; Liwei Shi; Xiufan Liu. 2021. "Assay of extracellular matrix degradation and transmigration of chicken peripheral blood mononuclear cells after infection with genotype VII Newcastle disease virus in vitro." Journal of Virological Methods 290, no. : 114076.
Replication of Newcastle disease virus (NDV) is regulated by various host mechanisms, but the role of the extracellular signal-regulated kinase (ERK) pathway in regulating NDV replication is an open question. In this study, the relationship between the ERK pathway and NDV replication was investigated. NDV activated the ERK signaling in chicken embryo fibroblasts at the late stage of infection, correlating to expression of viral proteins. Specific blockage of the ERK pathway activation significantly decreased the transcription and translation levels of viral genes as well as virus replication and the cytopathogenic effect caused by NDV. Our results demonstrate that activation of the ERK pathway is required for NDV replication.
Jie Ni; Shunlin Hu; Xiaoquan Wang; Xiaowen Liu; Zenglei Hu; Xiufan Liu. Activation of the extracellular signal-regulated kinase pathway is required for replication of Newcastle disease virus. Archives of Virology 2021, 166, 921 -927.
AMA StyleJie Ni, Shunlin Hu, Xiaoquan Wang, Xiaowen Liu, Zenglei Hu, Xiufan Liu. Activation of the extracellular signal-regulated kinase pathway is required for replication of Newcastle disease virus. Archives of Virology. 2021; 166 (3):921-927.
Chicago/Turabian StyleJie Ni; Shunlin Hu; Xiaoquan Wang; Xiaowen Liu; Zenglei Hu; Xiufan Liu. 2021. "Activation of the extracellular signal-regulated kinase pathway is required for replication of Newcastle disease virus." Archives of Virology 166, no. 3: 921-927.
The first avian H7N9 influenza outbreak in spring of 2013 emerged in an unprecedented transmission from infected poultry to humans in the Yangtze delta area, eastern China, posing a dual challenge to public health and poultry industry. However, the mechanism for how avian H7N9 influenza virus adapts to mammalian hosts has not been clearly understood. Here, to identify adaptive changes that confer enhanced virulence of H7N9 virus in mammals, we generated a mouse-adapted H7N9 variant virus (S8) by serial lung-to-lung passages of the wild-type SDL124 virus in mice and compared their phenotype in vivo and in vitro. Sequence analysis showed that the two viruses differed by 27 amino acids distributed among six genes, containing changes in PB2 (E627K, D701N) and HA (Q226L) genes. The 50% mouse lethal dose (MLD50) of S8 reduced about 500 folds, to be moderately pathogenic to mice when compared to that of low pathogenic wild-type SDL124. Moreover, S8 replicated efficiently in mouse lungs and displayed expanded tissue tropism, and induced a greater degree of pulmonary edema and higher level of inflammatory cell infiltration in bronchoalveolar lavage fluids than SDL124 did. Interestingly, the mouse adapted S8 virus obtained strong affinity for human-like (SAα-2,6 Gal) receptor during the adaptation in mice. Correspondingly, compared with SDL124 virus, S8 virus showed higher replication efficiency in mammalian cells, whereas lower replication ability in avian cells. Taken together, these findings suggest that these mutations synergistically elevate the ability of H7N9 virus to disseminate to multiple organs and subsequently enhance the virulence of H7N9 virus in mammalian hosts.
Guoqing Wang; Dong Liu; Jiao Hu; Min Gu; Xiaoquan Wang; Dongchang He; Lei Zhang; Jun Li; Xinxin Zheng; Zixiong Zeng; Huimou Liu; Shunlin Hu; Daxin Peng; Xinan Jiao; Xiufan Liu. Mutations during the adaptation of H7N9 avian influenza virus to mice lungs enhance human-like sialic acid binding activity and virulence in mice. Veterinary Microbiology 2021, 254, 109000 .
AMA StyleGuoqing Wang, Dong Liu, Jiao Hu, Min Gu, Xiaoquan Wang, Dongchang He, Lei Zhang, Jun Li, Xinxin Zheng, Zixiong Zeng, Huimou Liu, Shunlin Hu, Daxin Peng, Xinan Jiao, Xiufan Liu. Mutations during the adaptation of H7N9 avian influenza virus to mice lungs enhance human-like sialic acid binding activity and virulence in mice. Veterinary Microbiology. 2021; 254 ():109000.
Chicago/Turabian StyleGuoqing Wang; Dong Liu; Jiao Hu; Min Gu; Xiaoquan Wang; Dongchang He; Lei Zhang; Jun Li; Xinxin Zheng; Zixiong Zeng; Huimou Liu; Shunlin Hu; Daxin Peng; Xinan Jiao; Xiufan Liu. 2021. "Mutations during the adaptation of H7N9 avian influenza virus to mice lungs enhance human-like sialic acid binding activity and virulence in mice." Veterinary Microbiology 254, no. : 109000.
Since 2014, clade 2.3.4.4 has become the dominant epidemic branch of the Asian lineage H5 subtype highly pathogenic avian influenza virus (HPAIV) in southern and eastern China, while the H5N6 subtype is the most prevalent. We have shown earlier that lack of glycosylation at position 158 of the hemagglutinin (HA) glycoprotein due to the T160A mutation is a key determinant of the dual receptor binding property of clade 2.3.4.4 H5NX subtypes. Our present study aims to explore other effects of this site among H5N6 viruses. Here we report that N-linked glycosylation at site 158 facilitated the assembly of virus-like particles and enhanced virus replication in A549, MDCK, and chicken embryonic fibroblast (CEF) cells. Consistently, the HA-glycosylated H5N6 virus induced higher levels of inflammatory factors and resulted in stronger pathogenicity in mice than the virus without glycosylation at site 158. However, H5N6 viruses without glycosylation at site 158 were more resistant to heat and bound host cells better than the HA-glycosylated viruses. H5N6 virus without glycosylation at this site triggered the host immune response mechanism to antagonize the viral infection, making viral pathogenicity milder and favoring virus spread. These findings highlight the importance of glycosylation at site 158 of HA for the pathogenicity of the H5N6 viruses.
Ruyi Gao; Min Gu; Liwei Shi; Kaituo Liu; Xiuli Li; Xiaoquan Wang; Jiao Hu; Xiaowen Liu; Shunlin Hu; Sujuan Chen; Daxin Peng; Xinan Jiao; Xiufan Liu. N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses. Veterinary Research 2021, 52, 1 -14.
AMA StyleRuyi Gao, Min Gu, Liwei Shi, Kaituo Liu, Xiuli Li, Xiaoquan Wang, Jiao Hu, Xiaowen Liu, Shunlin Hu, Sujuan Chen, Daxin Peng, Xinan Jiao, Xiufan Liu. N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses. Veterinary Research. 2021; 52 (1):1-14.
Chicago/Turabian StyleRuyi Gao; Min Gu; Liwei Shi; Kaituo Liu; Xiuli Li; Xiaoquan Wang; Jiao Hu; Xiaowen Liu; Shunlin Hu; Sujuan Chen; Daxin Peng; Xinan Jiao; Xiufan Liu. 2021. "N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses." Veterinary Research 52, no. 1: 1-14.
As the causative agent of Newcastle disease (ND), Newcastle disease virus (NDV) has seriously restricted the development of the poultry industry. Previous research has shown that miRNAs, members of the small noncoding RNA family, are implicated in the regulation NDV replication through extensive interactions with host mRNAs, but whether miRNAs affect NDV replication by directly binding to the NDV antigenome remains unclear. In this study, potential Gallus gallus miRNAs targeting the antigenome of NDV were bioinformatically predicted using the online software RegRNA 2.0, and gga-miR-1603 and gga-miR-1794 were identified as targeting the viral L gene directly through dual-luciferase reporter assays. Sequence alignment analysis demonstrated that multiple genotypes of NDVs harbored highly conserved binding sites for gga-miR-1603 and gga-miR-1794 in the viral antigenome located at 8611–8634 nt and 14,490–14,514 nt, respectively. Meanwhile, we found that gga-miR-1603 and gga-miR-1794 negatively regulated the expression of viral L gene at both the RNA and protein levels, as well as viral replication in vitro. Furthermore, NDV infection had no effect on endogenous gga-miR-1603 and gga-miR-1794 expression in various avian cell lines. Overall, our present study demonstrated that gga-miR-1603 and gga-miR-1794 directly bind to the viral L gene to facilitate ts degradation and inhibit the replication of multiple genotypes of NDVs in vitro. These findings will provide us with important clues for antiviral therapy against NDV infection.
Yu Chen; Shanshan Zhu; Jiao Hu; Zenglei Hu; Xiaowen Liu; Xiaoquan Wang; Min Gu; Shunlin Hu; Xiufan Liu. gga-miR-1603 and gga-miR-1794 directly target viral L gene and function as a broad-spectrum antiviral factor against NDV replication. Virulence 2020, 12, 45 -56.
AMA StyleYu Chen, Shanshan Zhu, Jiao Hu, Zenglei Hu, Xiaowen Liu, Xiaoquan Wang, Min Gu, Shunlin Hu, Xiufan Liu. gga-miR-1603 and gga-miR-1794 directly target viral L gene and function as a broad-spectrum antiviral factor against NDV replication. Virulence. 2020; 12 (1):45-56.
Chicago/Turabian StyleYu Chen; Shanshan Zhu; Jiao Hu; Zenglei Hu; Xiaowen Liu; Xiaoquan Wang; Min Gu; Shunlin Hu; Xiufan Liu. 2020. "gga-miR-1603 and gga-miR-1794 directly target viral L gene and function as a broad-spectrum antiviral factor against NDV replication." Virulence 12, no. 1: 45-56.
Avian influenza virus (AIV) emerged and has continued to re-emerge, continuously posing great threats to animal and human health. The detection of hemagglutination inhibition (HI) or virus neutralization antibodies (NA) is essential for assessing immune protection against AIV. However, the HI/NA-independent immune protection is constantly observed in vaccines' development against H7N9 subtype AIV and other subtypes in chickens and mammals, necessitating the analysis of the cellular immune response. Here, we established a multi-parameter flow cytometry to examine the innate and adaptive cellular immune responses in chickens after intranasal infection with low pathogenicity H7N9 AIV. This assay allowed us to comprehensively define chicken macrophages, dendritic cells, and their MHC-II expression, NK cells, γδ T cells, B cells, and distinct T cell subsets in steady state and during infection. We found that NK cells and KUL01+ cells significantly increased after H7N9 infection, especially in the lung, and the KUL01+ cells upregulated MHC-II and CD11c expression. Additionally, the percentages and numbers of γδ T cells and CD8 T cells significantly increased and exhibited an activated phenotype with significant upregulation of CD25 expression in the lung but not in the spleen and blood. Furthermore, B cells showed increased in the lung but decreased in the blood and spleen in terms of the percentages or/and numbers, suggesting these cells may be recruited from the periphery after H7N9 infection. Our study firstly disclosed that H7N9 infection induced local and systemic cellular immune responses in chickens, the natural host of AIV, and that the flow cytometric assay developed in this study is useful for analyzing the cellular immune responses to AIVs and other avian infectious diseases and defining the correlates of immune protection.
Xiaoli Hao; Shuai Li; Lina Chen; Maoli Dong; Jiongjiong Wang; Jiao Hu; Min Gu; Xiaoquan Wang; Shunlin Hu; Daxin Peng; Xiufan Liu; Shaobin Shang. Establishing a Multicolor Flow Cytometry to Characterize Cellular Immune Response in Chickens Following H7N9 Avian Influenza Virus Infection. Viruses 2020, 12, 1396 .
AMA StyleXiaoli Hao, Shuai Li, Lina Chen, Maoli Dong, Jiongjiong Wang, Jiao Hu, Min Gu, Xiaoquan Wang, Shunlin Hu, Daxin Peng, Xiufan Liu, Shaobin Shang. Establishing a Multicolor Flow Cytometry to Characterize Cellular Immune Response in Chickens Following H7N9 Avian Influenza Virus Infection. Viruses. 2020; 12 (12):1396.
Chicago/Turabian StyleXiaoli Hao; Shuai Li; Lina Chen; Maoli Dong; Jiongjiong Wang; Jiao Hu; Min Gu; Xiaoquan Wang; Shunlin Hu; Daxin Peng; Xiufan Liu; Shaobin Shang. 2020. "Establishing a Multicolor Flow Cytometry to Characterize Cellular Immune Response in Chickens Following H7N9 Avian Influenza Virus Infection." Viruses 12, no. 12: 1396.
NS gene is generally considered to be related to the virulence of highly pathogenic avian influenza virus (AIV). In recent years, the strains with five amino acids added to the 80-84 positions of the NS1 protein have become prevalent in H5N1 subtype AIVs isolated from mammals. However, the pathogenicity and mechanism of this pattern in mammals remain unclear. In this study, H5N1 subtype AIVs without 80-84 amino acids of the NS1 protein (rNSΔ5aa ) and a mutant virus (rNS5aa-R ) with no deletion of 80-84 amino acids of the NS1 protein were used to determine the pathogenicity in mice. Our results showed that rNS5aa-R possessed an enhanced pathogenicity compared with rNSΔ5aa in vivo and in vitro, which was accompanied by high expression of IL-6, MX1 and CXCL10 in murine lungs. Furthermore, we found that rNS5aa-R increased the infection ability to dendritic cells (DCs). Besides, rNS5aa-R enhanced the expression of phenotypic markers (CD80, CD86, CD40 and MHCII), activation marker CD69, inflammatory cytokines (IL-6, TNF-α and IL-10) and antagonized interferon (IFN-α) of DCs, in comparison to rNSΔ5aa . Moreover, rNS5aa-R induced DCs to quickly migrate into nearby cervical lymph nodes by highly upregulating CCR7, and CD86 showed a high expression on the migrated DCs. We also found that rNS5aa-R -infected DCs significantly promoted the allogeneic CD4+ T-cell proliferation. These findings suggested that rNS5aa-R strongly induced the innate immune response compared with the rNSΔ5aa , which is conducive to activate a wide immune response, resulting in a strong cytokine storm and causing an enhanced pathogenicity of H5N1 subtype AIVs in mammals.
Sujuan Chen; Xinyu Miao; Dandan Huangfu; Xinyi Zhao; Minxia Zhang; Tao Qin; Daxin Peng; Xiufan Liu. H5N1 avian influenza virus without 80–84 amino acid deletion at the NS1 protein hijacks the innate immune system of dendritic cells for an enhanced mammalian pathogenicity. Transboundary and Emerging Diseases 2020, 1 .
AMA StyleSujuan Chen, Xinyu Miao, Dandan Huangfu, Xinyi Zhao, Minxia Zhang, Tao Qin, Daxin Peng, Xiufan Liu. H5N1 avian influenza virus without 80–84 amino acid deletion at the NS1 protein hijacks the innate immune system of dendritic cells for an enhanced mammalian pathogenicity. Transboundary and Emerging Diseases. 2020; ():1.
Chicago/Turabian StyleSujuan Chen; Xinyu Miao; Dandan Huangfu; Xinyi Zhao; Minxia Zhang; Tao Qin; Daxin Peng; Xiufan Liu. 2020. "H5N1 avian influenza virus without 80–84 amino acid deletion at the NS1 protein hijacks the innate immune system of dendritic cells for an enhanced mammalian pathogenicity." Transboundary and Emerging Diseases , no. : 1.
Janus kinase (JAK) inhibitors have been developed as novel immunomodulatory drugs and primarily used for treating rheumatoid arthritis and other inflammatory diseases. Recent studies have suggested that this category of anti-inflammatory drugs could be potentially useful for the control of inflammation “storms” in respiratory virus infections. In addition to their role in regulating immune cell functions, JAK1 and JAK2 have been recently identified as crucial cellular factors involved in influenza A virus (IAV) replication and could be potentially targeted for antiviral therapy. Gingerenone A (Gin A) is a compound derived from ginger roots and a dual inhibitor of JAK2 and p70 S6 kinase (S6K1). Our present study aimed to determine the antiviral activity of Gin A on influenza A virus (IAV) and to understand its mechanisms of action. Here, we reported that Gin A suppressed the replication of three IAV subtypes (H1N1, H5N1, H9N2) in four cell lines. IAV replication was also inhibited by Ruxolitinib (Rux), a JAK inhibitor, but not by PF-4708671, an S6K1 inhibitor. JAK2 overexpression enhanced H5N1 virus replication and attenuated Gin A-mediated antiviral activity. In vivo experiments revealed that Gin A treatment suppressed IAV replication in the lungs of H5N1 virus-infected mice, alleviated their body weight loss, and prolonged their survival. Our study suggests that Gin A restricts IAV replication by inhibiting JAK2 activity; Gin A could be potentially useful for the control of influenza virus infections.
Jiongjiong Wang; Richard A. Prinz; Xiufan Liu; Xiulong Xu. In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2. Viruses 2020, 12, 1141 .
AMA StyleJiongjiong Wang, Richard A. Prinz, Xiufan Liu, Xiulong Xu. In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2. Viruses. 2020; 12 (10):1141.
Chicago/Turabian StyleJiongjiong Wang; Richard A. Prinz; Xiufan Liu; Xiulong Xu. 2020. "In Vitro and In Vivo Antiviral Activity of Gingerenone A on Influenza A Virus Is Mediated by Targeting Janus Kinase 2." Viruses 12, no. 10: 1141.
A recent article by Gu in the Journal of Infection(1) reported two highly pathogenic H7N9 strains harboring the E627K mutation in the polybasic protein 2 (PB2) gene from chickens and showed that avian influenza viruses (AIVs) are evolving to adapt to humans. AIVs pose an important and ongoing threat to public health. Historically, both the highly pathogenic avian influenza viruses (H5N1, H5N6, H7N7, H7N3, and H7N9) and the lowly pathogenic avian influenza viruses (H7N2, H7N3, H9N2, H7N9, H6N1, H10N7, and H10N8) have caused sporadic human infections.
Kaituo Liu; Xiaoquan Wang; Daxiu Jiang; Naiqing Xu; Ruyi Gao; Wenwen Han; Min Gu; Jiao Hu; Xiaowen Liu; Shunlin Hu; Xiufan Liu. Pathogenicity and transmissibility of an H9N2 avian influenza virus that naturally harbors the mammalian-adaptive molecular factors in the hemagglutinin and PB2 proteins. Journal of Infection 2020, 82, e22 -e23.
AMA StyleKaituo Liu, Xiaoquan Wang, Daxiu Jiang, Naiqing Xu, Ruyi Gao, Wenwen Han, Min Gu, Jiao Hu, Xiaowen Liu, Shunlin Hu, Xiufan Liu. Pathogenicity and transmissibility of an H9N2 avian influenza virus that naturally harbors the mammalian-adaptive molecular factors in the hemagglutinin and PB2 proteins. Journal of Infection. 2020; 82 (2):e22-e23.
Chicago/Turabian StyleKaituo Liu; Xiaoquan Wang; Daxiu Jiang; Naiqing Xu; Ruyi Gao; Wenwen Han; Min Gu; Jiao Hu; Xiaowen Liu; Shunlin Hu; Xiufan Liu. 2020. "Pathogenicity and transmissibility of an H9N2 avian influenza virus that naturally harbors the mammalian-adaptive molecular factors in the hemagglutinin and PB2 proteins." Journal of Infection 82, no. 2: e22-e23.
PA-X is a fusion protein of influenza virus which plays a crucial role in modulating influenza virus-induced host innate immune response and subsequent pathogenicity. However, the potential mechanism of PA-X regulation of the host innate immune response remains largely unknown. It is well known that NF-κB signal pathway is crucial for the immediate early step of immune responses activation, while the specific role of PA-X in NF-κB transcriptional activity is totally unknown. In this study, we initially showed that PA-X inhibits NF-κB transcription that stimulated by poly(I:C). We then further determined that the inhibitory effect on NF-κB activation mediated by PA-X was characterized by restricting NF-κB p65 nuclear translocation and nuclear NF-κB p65 activity but not by impeding the phosphorylation of NF-κB p65. Correspondingly, PA-X decreases the amount of NF-κB signaling pathway-associated genes, including TNF-α, Nos2, IL-6 and IL-2. Moreover, PA-X also suppresses both the mRNA and protein expression level of IFN-β, suggesting the direct contribution of PA-X to the inhibition of NF-κB-regulated IFN-β expression. Together, our study sheds light on the potential molecular mechanisms underlying the regulation of host NF-κB activity by PA-X and also identifies a novel functional role for PA-X in counteracting the host innate immune response. However, further exploration of the more elaborate mechanism of PA-X-mediated inhibition of NF-κB activity and the associated signaling pathway may help to elucidate its precise mechanism of evading and subverting the host immune response.
Jiao Hu; Ming Kong; Zhu Cui; Zhao Gao; Chunxi Ma; Zenglei Hu; Xinan Jiao; Xiufan Liu. PA-X protein of H5N1 avian influenza virus inhibits NF-kappaB activity, a potential mechanism for PA-X counteracting the host innate immune responses. Veterinary Microbiology 2020, 250, 108838 .
AMA StyleJiao Hu, Ming Kong, Zhu Cui, Zhao Gao, Chunxi Ma, Zenglei Hu, Xinan Jiao, Xiufan Liu. PA-X protein of H5N1 avian influenza virus inhibits NF-kappaB activity, a potential mechanism for PA-X counteracting the host innate immune responses. Veterinary Microbiology. 2020; 250 ():108838.
Chicago/Turabian StyleJiao Hu; Ming Kong; Zhu Cui; Zhao Gao; Chunxi Ma; Zenglei Hu; Xinan Jiao; Xiufan Liu. 2020. "PA-X protein of H5N1 avian influenza virus inhibits NF-kappaB activity, a potential mechanism for PA-X counteracting the host innate immune responses." Veterinary Microbiology 250, no. : 108838.
PB2 E627K mutation of influenza A virus has been considered relevant to increased mammalian virulence and adaptation. In H7N9, the substitution is naturally confined to most human isolates and few low pathogenic avian isolates. However, we isolated two highly pathogenic H7N9 variants harboring PB2 627K from chickens in northern China.
Jinyuan Gu; Min Gu; Yayao Yan; Kaituo Liu; Xiaoquan Wang; Xiulong Xu; Xiufan Liu. Detection of PB2 627 K mutation in two highly pathogenic isolates of the H7N9 subtype Influenza a virus from chickens in Northern China. Journal of Infection 2020, 81, 979 -997.
AMA StyleJinyuan Gu, Min Gu, Yayao Yan, Kaituo Liu, Xiaoquan Wang, Xiulong Xu, Xiufan Liu. Detection of PB2 627 K mutation in two highly pathogenic isolates of the H7N9 subtype Influenza a virus from chickens in Northern China. Journal of Infection. 2020; 81 (6):979-997.
Chicago/Turabian StyleJinyuan Gu; Min Gu; Yayao Yan; Kaituo Liu; Xiaoquan Wang; Xiulong Xu; Xiufan Liu. 2020. "Detection of PB2 627 K mutation in two highly pathogenic isolates of the H7N9 subtype Influenza a virus from chickens in Northern China." Journal of Infection 81, no. 6: 979-997.
In recent years in China, clade 2.3.4.4 H5N6 plus clade 2.3.2.1 H5N1 subtype highly pathogenic avian influenza (HPAI) viruses have gradually become endemic in poultry, and their co‐circulation could inevitably facilitate the gene reassortment between each other. During our routine surveillance in live poultry markets (LPMs) in Eastern China in 2017‐2018, a novel reassortant H5N6 strain with the HA gene derived from clade 2.3.2.1 was isolated from the cloacal swabs of apparently healthy ducks. Phylogenetic tracing analysis indicated that another two clade 2.3.2.1 H5N1 strains with divergent lineages of PB1 gene and one clade 2.3.4.4 H5N6 isolate of the dominant genotype sharing spatio‐temporal proximity were intimately involved in the generation of this rarely reported clade 2.3.2.1 H5N6 reassortant. Distinct with the other three HPAI H5 viruses showing moderate virulence in mice, the H5N1 strain of the homologous internal‐gene constellation against the clade 2.3.2.1 H5N6 reassortant was highly pathogenic which might probably attribute to the H3 subtype‐derived PB1 gene. However, as compared to the clade 2.3.4.4 H5N6 ancestor, the clade 2.3.2.1 H5N6 reassortant displayed a broader tissue distribution and higher viral titers in mice, which could likely facilitate the viral maintenance and spread in nature. Therefore, our results highlight that continuous epidemiological survey of H5 subtype HPAI viruses in LPMs need to be strengthened to prevent the potential poultry or even public health threat of the novel reassortants from endemic viruses.
Zhichuang Ge; Min Gu; Tianyu Cai; Kaituo Liu; Ruyi Gao; Dong Liu; Wenqiang Sun; Xiuli Li; Lei Shi; Jiao Liu; Xiaoquan Wang; Jiao Hu; Xiaowen Liu; Shunlin Hu; Sujuan Chen; Daxin Peng; Xinan Jiao; Xiufan Liu. Phylogenetic tracing and biological characterization of a novel clade 2.3.2.1 reassortant of H5N6 subtype avian influenza virus in China. Transboundary and Emerging Diseases 2020, 68, 730 -741.
AMA StyleZhichuang Ge, Min Gu, Tianyu Cai, Kaituo Liu, Ruyi Gao, Dong Liu, Wenqiang Sun, Xiuli Li, Lei Shi, Jiao Liu, Xiaoquan Wang, Jiao Hu, Xiaowen Liu, Shunlin Hu, Sujuan Chen, Daxin Peng, Xinan Jiao, Xiufan Liu. Phylogenetic tracing and biological characterization of a novel clade 2.3.2.1 reassortant of H5N6 subtype avian influenza virus in China. Transboundary and Emerging Diseases. 2020; 68 (2):730-741.
Chicago/Turabian StyleZhichuang Ge; Min Gu; Tianyu Cai; Kaituo Liu; Ruyi Gao; Dong Liu; Wenqiang Sun; Xiuli Li; Lei Shi; Jiao Liu; Xiaoquan Wang; Jiao Hu; Xiaowen Liu; Shunlin Hu; Sujuan Chen; Daxin Peng; Xinan Jiao; Xiufan Liu. 2020. "Phylogenetic tracing and biological characterization of a novel clade 2.3.2.1 reassortant of H5N6 subtype avian influenza virus in China." Transboundary and Emerging Diseases 68, no. 2: 730-741.